Bile acid-polymer-probucol microparticles: protective effect on pancreatic β-cells and decrease in type 1 diabetes development in a murine model

Abstract

Studies in our laboratory have shown potential applications of the anti-atherosclerotic drug probucol (PB) in diabetes due to anti-inflammatory and β-cell protective effects. The anti-inflammatory effects were optimized by incorporation of the anti-inflammatory bile acid, ursodeoxycholic acid (UDCA). This study aimed to test PB absorption, tissue accumulation profiles, effects on inflammation and type 1 diabetes prevention when combined with UDCA. Balb/c mice were divided into three equal groups and gavaged daily PB powder, PB microcapsules or PB-UDCA microcapsules for one week, at a constant dose. Mice were injected with a single dose of intraperitoneal/subcutaneous alloxan to induce type-1 diabetes and once diabetes was confirmed, treatments were continued for 3 days. Mice were euthanized and blood and tissues collected for analysis of PB and cytokine levels. The PB-UDCA group showed the highest PB concentrations in blood, gut, liver, spleen, brain, and white adipose tissues, with no significant increase in pancreas, heart, skeletal muscles, kidneys, urine or feces. Interferon gamma in plasma was significantly reduced by PB-UDCA suggesting potent anti-inflammatory effects. Blood glucose levels remained similar after treatments, while survival was highest among the PB-UDCA group. Our findings suggest that PB-UDCA resulted in best PB blood and tissue absorption and reduced inflammation.

Keywords:

• Type-1 diabetes
• probucol
• nanoencapsulation technology
• bile acids
• ursodeoxycholic acid

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Al-Salami H has been and is currently receiving funding from Beijing Nat-Med Biotechnology Co. Ltd. The use of laboratory equipment, scientific and technical assistance of Microscopy and Microanalysis Facility at Curtin University which has been partially funded by the University, State and Commonwealth Governments. The work is partially supported by the European Union Horizon 2020 MEDLEM research project and innovation program under the Marie Skłodowska-Curie Grant Agreement No. 690876.